Bacteria are able to activate the terminal complement components, C3-9, and create phlogistic fragments by at least two different pathways: the classical pathway, involving antibody, C2, C4 and C2 and the alternative pathway. Our studies are involved in the following aspects of the interaction of bacteria and the alternative pathway: 1) the study of the role of the alternative pathway in host defense against infection, and 2) the bacterial components responsible for activation of the alternative pathway, and 3) the defect in alternative pathway function in children with sickle cell disease. These studies are aimed at elucidating the role of the alternative pathway in natural immunity and its biological significance. BIBLIOGRAPHIC REFERENCES: Winkelstein, J.A. and Swift, A.J.: Host defense against the pneumococcus in T-lymphocyte deficient, nude mice. Infect and Immun. 12:1222, 1975. Winkelstein, J.A., Bocchini, J., Jr., and Schiffman, G.: Role of the capsular polysaccharide in the activation of the alternate pathway by the pneumococcus. J. Immunol. 116: 367, 1976.